The proposed studies are designed to evaluate the pharmacokinetic parameters and possible toxic effects of various doses of aminopterin with the maximum tolerated dose of the drug (i.e., causing minimal toxicity and ample fluid intake). Attempts will be made to correlate: a) dose with plasma levels of the drug, b) plasma level (and/or dose) with toxicity, c) plasma level (and/or dose) and efficacy of the drug, d) renal function with renal clearance of the drug, e) renal clearance or total body clearance with toxicity. Patients will be hydrated and the urine will be made alkaline (NaHCO3). Aminopterin (25 mg/sq.m) will be given as a single iv bolus to 3 patients followed at 24 hr by citrovorum "rescue". Other patients in groups of 3 will then receive higher doses (50, 100, 150, 200 mg/sq.m etc.). When a dose level is reached which can be tolerated with minimal toxicity, 3 additional patients will receive that dose. Studies will then be carried out with 6- and 24-hr continuous iv infusion. The concentration of aminopterin will be measured (by radioimmunoassay) in plasma, red cells, urine, and other biological materials (if available). Complete blood and urine analyses will be carried out. Pharmacokinetic parameters will be determined and any relationship between clinical and/or toxicological response with the pharmacokinetic data will be evaluated.